• Medientyp: E-Artikel
  • Titel: Sugar‐Derived Ras Inhibitors: Group Epitope Mapping by NMR Spectroscopy and Biological Evaluation
  • Beteiligte: Peri, Francesco; Airoldi, Cristina; Colombo, Sonia; Mari, Silvia; Jiménez‐Barbero, Jesús; Martegani, Enzo; Nicotra, Francesco
  • Erschienen: Wiley, 2006
  • Erschienen in: European Journal of Organic Chemistry, 2006 (2006) 16, Seite 3707-3720
  • Sprache: Englisch
  • DOI: 10.1002/ejoc.200600132
  • ISSN: 1434-193X; 1099-0690
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  • Beschreibung: AbstractNovel inhibitors of Ras protein activation have been found, containing a bicyclic core derived from D‐arabinose and benzyl and phenylhydroxylamine moieties. NMR studies (trNOE, saturation‐transfer difference, STD) of the binding between these molecules and human p21 h‐Ras are reported. A pharmacophore mapping indicates that both the benzyl and the phenylhydroxylamine moieties are essential for protein binding. Molecules lacking one of these groups were synthesized and tested to confirm this hypothesis, and no interaction with Ras in vitro, nor biological activity in mammalian cells was observed. Our studies led to the development of molecules that selectively inhibit Ras‐dependent cellular growth in mammalian cells. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)